This project seeks to define the spectrum of acute, latent and recurrent CNS and PNS disease produced by experimental herpesvirus infections, particularly herpes simplex virus 2 (HSV-2), and to refine and test a hypothesis which relate HSV-2 infection to human demyelinative disease, including multiple sclerosis (MS). Our previous studies suggest that several features of HSV epidemiology and pathology are consistent with a possible etiological role for this agent in MS. During FY 1988, studies performed show that HSV-related antigen previously found in human demyelinative lesions does not appear to be related to human cytomegalovirus or varicella-zoster virus. Efforts were begun to more precisely identify the antigen detected and to provide independent evidence of virus presence in lesions. In experimental models, reactivated HSV-2 infection has been induced using high-dose immunosuppression. Targets of reactivated infection in mice with latent infection established by intracerebral inoculation of virus include CNS and PNS tissues, as well as a variety of peripheral, non-neural tissues. This is the first animal model in which the CNS is shown to be an important target of reactivated HSV infection.